Defining risk drinking.

Many efforts to prevent alcohol-related harm are aimed at reducing risk drinking. This article outlines the many conceptual and methodological challenges to defining risk drinking. It summarizes recent evidence regarding associations of various aspects of alcohol consumption with chronic and acute alcohol-related harms, including mortality, morbidity, injury, and alcohol use disorders, and summarizes the study designs most appropriate to defining risk thresholds for these types of harm. In addition, it presents an international overview of low-risk drinking guidelines from more than 20 countries, illustrating the wide range of interpretations of the scientific evidence related to risk drinking. This article also explores the impact of drink size on defining risk drinking and describes variation in what is considered to be a standard drink across populations. Actual and standard drink sizes differ in the United States, and this discrepancy affects definitions of risk drinking and prevention efforts.

P reventing alcoholrelated harm does not necessarily require that risk drinking be defined. At the population level, harm reduction can be achieved through numerous broad measures that determine the price or availability of beverage alcohol (Babor et al. 2003). Measures such as these affect drinkers at all consumption levels. Although there is inconsistent evidence as to whether their impact is greater among heavy or lighttomoderate drinkers (Farrell et al. 2003;Gmel et al. 2008;Heeb et al. 2003;Mäkelä et al. 2008;Manning et al. 1995;Wagenaar et al. 2009), such measures have proven to be effective in reducing problems associated with heavy or problem drinking (Wagenaar et al. 2009(Wagenaar et al. , 2010. In contrast to such global approaches, targeted approaches focus on preventing, identifying, and modifying risk drinking (i.e., drinking at levels or in patterns that increase the risk of alcoholrelated harm). The development and dissemi nation of drinking guidelines that define the limits of lowrisk alcohol consump tion are one example of this type of prevention effort. Defining risk drink ing may seem simple compared with preventing it, but in fact there are many conceptual and methodological chal lenges to arriving at a definition of risk drinking.
Perhaps the most essential challenge lies in determining the threshold that discriminates "lowrisk" and "risk" drinking. Is risk drinking any consump tion that corresponds to a significantly higher level of harm than that experi enced by lifetime abstainers, or does the harm have to be of a specified magnitude? Given a linear relationship between consumption and harm, where is the appropriate cutoff point? Beyond this basic question, one must also ask what types of harms should be con sidered. Excessive use of alcohol is associated with a wide range of harmful outcomes, including alcohol use dis orders; mortality and morbidity from chronic medical conditions, such as alcoholic liver disease, and acute causes, such as vehicular crashes and accidental and intentional injury; and a host of social and legal problems. Should risk drinking definitions be keyed more closely to those types of harm most strongly attributable to alcohol use, or to the most severe harms (i.e., mortality or years of life lost) regardless of the strength of their association with drinking?
What aspects of alcohol consumption should be used to define risk drinking? Should these vary according to the type of harm (e.g., drinking volume in relation to chronic conditions, and drinking pattern in relation to acute alcoholrelated harm)? Should risk drinking be defined in terms of con sumption that reflects current alcohol related problems, as is the case with screening for alcohol use disorders and emergencydepartment studies of drinking in relation to the risk of injury? Or should it be defined in terms of consumption that increases the risk of developing alcoholrelated harm in the long term, as is the case with prospective studies of alcohol related mortality and morbidity?
What types of studies are most appropriate for assessing associations between different aspects of alcohol DEBORAH A. DAWSON, PH.D., is a former staff scientist at the Laboratory of Epidemiology and Biometry, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland.

consumption and alcoholrelated harm?
To what extent should we account for the quality of the consumption data upon which evidence of alcoholrelated harm is based? Many of the large prospective studies used to assess mortality risk collect data on numerous putative risk factors, and they often contain too few questions on alcohol use to yield estimates of consumption that fully capture the contribution of heavy drinking days or multiple bev erage types. If it is likely that associa tions of consumption with the risk of harm are based on underestimates of consumption, how should we account for that fact when using the data to inform definitions of risk drinking?
Finally, what is the appropriate cut off between enough information and too much? Should definitions of risk drinking, or, conversely, lowrisk drink ing guidelines, be complex enough to include volume and patternrelated risks and their variation across popu lation subgroups or should they be simple enough so that drinkers can easily recall them and clinicians can easily identify risk drinkers based on a single metric? Many guidelines con tain different limits for men and women; others stipulate lower limits for the youngest and oldest drinkers. In addition, some guidelines explicitly mention groups of individuals for whom any drinking is inadvisable (e.g., women who are pregnant or trying to become pregnant, people intending to drive or operate complex machinery, or individuals with medical conditions or taking medication). These exceptions to the general guidelines might also include individuals with former alcohol problems or those with a history of treatment for alcohol use disorders. Is it appropriate to use the same defi nition of risk drinking for all prevention efforts, or should the context determine the relative emphasis on different aspects of risk drinking? How should we account for variation across beverages and drinkers in drink size and alcohol content when defining risk drinking?
These questions provide some notion of the complex challenges posed in defining risk drinking and illustrate why there is no absolute consensus on the most appropriate definition. The following sections describe the evidence for associations of drinking volume and pattern with alcoholrelated harm, issues surrounding standard drink size, and the conclusions drawn by selected countries in defining risk drinking in their national drinking guidelines.

Association of Drinking Volume With Alcohol Related Harm
Drinking volume, generally character ized in terms of average daily volume (ADV) of alcohol intake, has been widely studied in association with mortality and chronic disease morbid ity in large prospective cohort studies. Because a full review of this extensive literature lies beyond the scope of this article, this section will summarize the findings of selected metaanalyses conducted in 2000 or more recently. The focus will be on studies with doseresponse curves that can be used to inform riskdrinking definitions, rather than studies that summarize associations by means of alcohol attributable fractions (i.e., the propor tions of deaths from selected causes attributable to drinking) or years of life lost (e.g., Gutjarh et al. 2001;Rehm et al. 2003Rehm et al. , 2006Rehm et al. , 2007Rehm et al. , 2009). More over, because the focus is on the defi nition of risk drinking, this article will not examine levels of drinking volume for which supposedly protective effects (i.e., risk levels lower than those of abstainers) have been observed.
Di Castelnuovo and colleagues (2006) conducted a metaanalysis of 34 prospective studies of allcause mortality and established 56 indepen dent risk curves reflecting various models and population subgroups. Visual inspection of the pooled adjusted risk curves for studies that presented both unadjusted and adjusted associa tions, including confidence intervals, suggests that the mortality risk began to significantly exceed the level of nondrinkers at an ADV of approxi mately 38 g of ethanol (or about 2.7 standard drinks). A similar threshold was observed for pooled studies that excluded occasional and former drinkers from the reference group, irrespective of the level of adjustment. Gender specific curves, regardless of the level of control or reference group charac teristics, showed that the risk of all cause mortality started to increase at a lower ADV for women (approxi mately 35 g) than men (approximate ly 45 g). However, it has been argued that exclusion of studies biased by misclassification error with respect to the abstainer category might have yielded lower thresholds for harm (Fillmore et al. 2007). In a meta analysis of allcause mortality studies conducted before 2000, Gmel and colleagues (2003) reported a significant increase in risk relative to lifetime abstainers at ADVs of 30 g to 50 g for women (relative risk 1 [RR]: 1.40) and at ADVs of 40 g to 70 g for men (RR: 1.04), based on studies where the mean age of the respondents was at least 45 years at baseline.
In terms of diseasespecific morbidity and mortality, much of the literature concerning coronary heart disease (CHD), stroke, and type 2 diabetes has centered on the debate concerning possible protective effects of moderate volumes of intake, but some meta analyses have reported increased risks of these diseases at heavy volumes of consumption. A metaanalysis of 28 CHD studies by Corrao and colleagues (2004) indicated an increased risk compared with nondrinkers at an ADV of 89 g. Corrao and colleagues observed increased risks of hemor rhagic stroke at ADVs of 50 g and higher in the metaanalyses of six studies and of ischemic stroke at an ADV of 100 g in the metaanalyses of three studies. These findings for stroke risk are consistent with those of Reynolds and colleagues (2003), who conducted a metaanalysis of 35 cohort and casecontrol studies of stroke risk. They reported a signifi cantly increased risk of all types of stroke at ADVs of 60 g and higher, 1 Relative risk is a ratio of the probability of the event occurring in the exposed group versus a nonexposed group. For example, a relative risk of 10 means that the exposed group is 10 times more likely than the nonexposed group to experience the event.
with an RR that was twice as great for women as men (RR: 4.29 vs. RR: 1.76) at those volumes of intake. With respect to type 2 diabetes, results of metaanalyses have been inconsistent. At low thresholds for heavy drinking, neither Koppes and colleagues (2005) nor Carlsson and colleagues (2005) found any increased risk. However, a more recent metaanalysis by Baulina and colleagues (2009) of 20 cohort studies found that the risk of type 2 diabetes increased for men at an ADV of approximately 60 g and for women at an ADV of approximately 50 g. Corrao and colleagues (2004) report ed a linear doseresponse function for essential hypertension on the basis of a metaanalysis of two studies, with significantly increased risks correspond ing to ADVs as low as 25 g (RR: 1.43, increasing to 2.04 at an ADV of 50 g and to 4.15 at an ADV of 100 g). In a larger metaanalysis of 12 cohort studies, Taylor and colleagues (2009) reported significant RRs of 1.57 for men and 1.81 for women at an ADV of 50 g and of 2.47 for men and 2.82 for women at an ADV of 100 g. Neither of these metaanalyses reported specific cut points at which the risk of hypertension was increased. Other nonneoplastic conditions (i.e., non cancerous conditions) for which linear dose functions were observed, at least up to an AVD of 100 g, included chronic pancreatitis and liver cirrhosis. For both of these conditions, the risk was significantly increased at an ADV of 25 g (RR: 1.34 and 2.90, respec tively; Corrao et al. 2004). In one prospective study that presented gender specific risk curves, the risk of all types of liver disease increased at a lower volume of alcohol intake for women (7 to 13 drinks per week) than men (14 to 27 drinks per week).
In a metaanalysis of six studies of pancreatitis, Irving and colleagues (2009) reported a monotonic and approximately exponential dose response relationship between the ADV and the risk of pancreatitis. On the basis of a continuous risk curve, the risk of pancreatitis was significantly increased at an ADV of 36 g (RR: 1.2), but categorical models found that the association was not significantly increased until the ADV reached levels greater than 48 g (RR: 2.5). Chong and colleagues (2008), who conducted a metaanalysis of seven cohort studies examining alcohol consumption and agerelated macular degeneration, found an increased risk of earlystage macular degeneration at an ADV of greater than 30 g (odds ratio [OR]: 1.47); however, the association with ADV was not significant for latestage macular degeneration.
Finally, in terms of neoplastic con ditions, Corrao and colleagues (2004) reported significantly increased risks of oral, pharyngeal, esophageal, laryn geal, colon, rectal, liver, and breast cancers at ADVs of 25 g and greater.
Other metaanalyses have reported RRs for laryngeal cancer relative to nondrinkers of 1.94 at an ADV of 50 g and of 3.95 at an ADV of 100 g (Altieri et al. 2005) and RRs for col orectal cancer of 1.41 at ADVs of 45 g and greater, with an RR of 1.16 that fell just short of significance for ADVs of 30 g to 44 g (Cho et al. 2004). Increased risks of breast cancer also have been reported at an ADV of 12 g (RR: 1.06; Ellison et al. 2001) and 35 g to 44 g (RR: 1.32; Hamajima et al. 2002).

Association of Drinking Pattern With Alcohol Related Harm
For some types of alcoholrelated harm, notably those that reflect acute conse quences of heavydrinking occasions, average volume of intake is a less rele vant risk factor than measures of alcohol use directly associated with the event (i.e., drinking in the event) or of heavy episodic drinking patterns. Drinking in the event is typically measured by means of a positive blood alcohol content (BAC) result or self report of drinking in the 6 hours preceding an injury or medical prob lem. Heavy episodic drinking (HED), sometimes called risky singleoccasion drinking (RSOD; Gmel et al. 2011) or binge drinking, traditionally has been defined-at least in the United States-as consuming five or more drinks in a single day or a single drinking occasion. However, a defini tion based on five or more drinks for men and four or more drinks for women (Wechsler and Nelson 2001;Wechsler et al. 1995) has come into increasing use in recent decades. Although the scientific basis for defining HED as five or more drinks is some what obscure, the definition of five or more drinks (for men) or four or more drinks (for women) is supported by its close correlation with the amount of ethanol required to achieve a BAC of 0.75 g to 0.80 g per kg of body weight (Dawson et al. 1996). Such concentrations have been shown to be associated with psychomotor and cognitive impairment in experimental studies (Hindenmarch et al. 1991;Lane et al. 2004). The associations of harm with drinking in the event and HED measures have been assessed using a wide variety of study designs, including casecontrol, case crossover, and experimental blood alcohol level doseresponse studies, in addition to crosssectional and prospective analyses of general population data.
Emergencydepartment studies have been a major source of data on the association between drinking and the likelihood of injury severe enough to warrant treatment at an emergency department (see the review in Cherpitel 2007). Casecontrol studies, which examine the odds of presenting at an emergency department with an injury as opposed to a non-injuryrelated medical problem, have shown that the odds of injury are increased at even low volumes of consumption (e.g., one drink a week) and with any fre quency of drinking five or more drinks on any single occasion. However, the risk curves from the Emergency Room Collaborative Alcohol Analysis Project (ERCAAP) showed a tendency to level off at volumes of ethanol intake greater than two drinks per day, or drinking five or more drinks on any single occasion more often than monthly. Although the shapes of the risk curves were similar for men and women, injury risks were lower at comparable drinking levels for women than men (Cherpitel et al. 2006). In contrast, an Australian casecontrol study of individuals hospitalized for injury paired with community con trol subjects found significantly high er risks of injury among women with an intheevent intake of more than 60 g of ethanol (Stockwell et al. 2002). In general, the risk of injury is more strongly associated with drinking in the event than with regular drinking patterns. In fact, a metaanalysis of emergencydepartment studies demon strated that pooled attributable risk sizes were 43 percent for drinking in the event compared with just 27 percent for usual drinking pattern (Cherpitel et al. 2005). Pooled data from the ERCAAP showed that indi viduals who tested positive for drinking in the event were more than 50 percent more likely to present for an injury as opposed to a medical problem (Cherpitel et al. 2003).
Individual case crossover studies, in which an individual's selfreported regular drinking pattern during some specified period is used as the "control" for his or her selfreported drinking in the event (Maclure 1991), have shown three to fourfold increases in the risk of injury in association with drinking in the event (Borges et al. 2004;Vinson et al. 2003a). One study showed the excess risk increasing directly with the number of drinks consumed from an OR of 1.8 for one to two drinks to an OR of 17.0 for seven or more drinks (Vinson et al. 2003b). Pooled data from 28 emergency department studies in 16 countries showed that the random pooled effect of drinking in the event compared with usual drinking was an increase of 5.69 in the likelihood of injury (Borges et al. 2006). Associations with drinking in the event are even stronger for violencerelated injuries than for all injuries, with a case crossover study showing a 34fold increase in the risk for a violencerelated injury associated with drinking in the event relative to drinking the previous day and a 10 fold increase relative to drinking in the previous month (Vinson et al. 2003a). The ERCAAP data also indicated that the odds of a violence related injury as opposed to an unin tentional one were increased by a fac tor of 5.5 at BACs of 0.15 to 0.199 (Macdonald et al. 2005). Evidence of gender differences was mixed. Associations of drinking in the event with violent versus unintentional injury were greater for men than women in Argentina, Belarus, and Spain but greater for women than for men in China. There were no gender differ ences with respect to drinking in the event in the United States, but the association between frequent HED and violent injury was greater among American women than men (OR: 4.52 vs. 1.63) (Wells et al. 2007).
Because deaths from external causes generally reflect drinking in the event of a fatal injury, analyses of the role of alcohol in such deaths have focused more strongly on drinking pattern than average volume of ethanol intake. In a prospective study of Russian men aged 25 to 64 years, with an average followup of 9.5 years, usual con sumption of at least 160 g of alcohol per occasion increased the risk of death from external causes by a factor of 2.08 compared with a usual con sumption of less than 80 g among individuals who drank at least once a month. A similar prospective study of Finnish men found that those who usually drank six or more bottles of beer per drinking occasion had a far higher risk of death from external causes than those who usually con sumed less than three bottles (RR: 7.10), even after adjusting for total consumption (Kauhanen et al. 1997). No significant increase in risk was observed at lower usual levels of intake (Malyutina et al. 2002). In a study of fatal injury that entailed matching death records with data from a series of Finnish alcohol surveys, consuming five or more drinks 25 to 52 times per year and more than 52 times per year were associated with fatal injury RRs of 2.63 and 5.78, respectively, relative to never consuming five or more drinks, even after adjusting for frequencies of drinking fewer than five drinks (Paljärvi et al. 2005). Dawson (2001) also found an increased risk of mortality from external causes in association with usual consumption of five or more drinks among U.S. adults, but only among those who drank this amount less than once a month. In a study of singlevehicle motor vehicle crashes, Heng and col leagues (2006) reported that the risk of fatality was significantly increased even at BACs associated with fairly low levels of intheevent consump tion (e.g., at BACs as low as 0.010 to 0.019 for drinkers ages 16 to 20).
Although most studies of chronic disease and allcause mortality have focused on the association with volume of ethanol intake, as described previ ously, a limited number of studies have examined associations with drinking pattern measures, primarily HED. Tolsrup and colleagues (2004) found that the allcause mortality risk associated with drinking 21 or more drinks a week was greater among people with infrequent as opposed to frequent intake (the former implying more drinks per drinking occasion) in a prospective Danish cohort study. On the basis of a Finnish cohort study of men ages 25 to 64, Laatikainen and colleagues (2003) found that the prospective risk of allcause mortality was 57 percent higher among men who had consumed six or more drinks at a time than among those who had not, even after controlling for volume of consumption. Another Finnish cohort study reported that men who usually drank six or more beers per occasion had higher risks of allcause mortality and fatal myocardial infarc tion than those who usually consumed fewer than three beers (RR: 3.01 and 6.50, respectively), independent of their total volume of consumption (Kauhanen et al. 1997). Mäkelä and colleagues (2005), who linked Finnish alcohol survey participants with death records, found an increased risk of allcause mortality among men in association with a high volume of ethanol intake consumed on heavy drinking occasions, but not in associ ation with a high volume consumed on lighterdrinking occasions. This relationship did not extend to women. In a 3.8year followup of patients hospitalized for myocardial infarction, those who had consumed three or more drinks within a 1 to 2hour period at least once in the past year were twice as likely to have died as those who had not (OR: 2.1 after adjusting for usual alcohol intake; Mukamal et al. 2005). Rivara and colleagues (2004), who applied etiologic fractions (the proportion of the cases caused by exposure) for alcoholattributable mortality to data from a series of crosssectional surveys of the U.S. general population, reported that more than onehalf of the deaths attributed to harmful drinking in the United States were a result of HED rather than medium to high volumes of intake.
In a metaanalysis of six studies that included drinking pattern and volume measures, Bagnardi and colleagues (2008) found an increased risk of car diovascular disease among drinkers compared with nondrinkers at a weekly average of 131 g among individuals who drank twice a week or less often (implying an intake of at least 65.5 g on drinking days). This same study did not find an increased CHD risk at even the highest weekly volumes among those who drank more regu larly. In a crosssectional analysis of drinking pattern and the prevalence of coronary calcification at the 15 year followup of a cohort study of young adults ages 18 to 30 at base line, having consumed five or more drinks at least once in the past month was associated with a significantly increased risk of calcification (OR: 2.1) independent of volume of intake. In an 8year followup of a Canadian population sample, the hazard rate of CHD mortality and morbidity was significantly increased among men (hazard rate ratio 2 [HRR]: 2.26) and women (HRR: 1.10) who had consumed eight or more drinks on at least one occasion in the past year, independent of mean volume of intake. For men only, consumption of eight or more drinks in the past year also was associated with a modest increase in morbidity and mortality from hypertension (HRR: 1.57; Murray et al. 2002). A Finnish cohort study of twins followed for 25 years found that monthly or more frequent con sumption of five or more drinks in midlife was associated with a more than threefold increase in the risk of devel oping dementia (Jarvenpaa et al. 2005).
Among the other types of alcohol related harm that have been associated with HED or high BAC concentra tions in experimental, crosssectional, and prospective surveys are violence (Brewer and Swahn 2005), including intimatepartner violence (see reviews in Foran and O'Leary 2008;Marshal 2003) and other forms of victimization (e.g., Connor et al. 2009;Stickley and Pridemore 2009;Testa and Livingston 2009;Wells and Thompson 2008); social and legal problems (e.g., Dawson et al. 2008: Rehm andGmel 1999;Viner and Taylor 2007;Wechsler and Nelson 2001); physical and mental quality of life (Green et al. 2004;Okoro et al. 2004); various aspects of cognitive functioning, including impaired judgment and risk taking (Breitmeier et al. 2007: Cairney et al. 2007Goudriaan et al. 2007;Lane et al. 2004;Neal and Fromme 2007); and fetal alcohol spectrum disorders (FASD) resulting from maternal drinking during pregnancy (Bailey and Sokol 2008;Testa et al. 2003). Consistent with the previously cited studies, these studies generally reported linear risk curves, sometimes with a threshold effect and often with signif icantly increased risks at relatively low frequencies of HED or usual/inthe event quantities of drinks consumed.

Associations of Drinking Volume and Pattern With Alcohol Use Disorders
Associations of drinking volume and pattern with alcohol use disorders (AUDs) have been established in both crosssectional and prospective designs. Studies of generalpopulation samples have shown that both the average vol ume of consumption and the absolute or relative frequency of heavy drinking are independently associated with the risk of alcohol abuse and dependence (e.g., see Caetano et al. 1997;Dawson and Archer 1993;Dawson et al. 1995;Midanik et al. 1996;Rehm et al. 2005). In a study of U.S. pastyear drinkers that examined daily drinking limits of no more than four drinks for men and three drinks for women and weekly drinking limits of no more than 14 drinks for men and 7 drinks for women, where drinks were defined as the equivalent of 0.6 oz of ethanol, the prevalence of alcohol dependence showed a linear increase with the fre quency of exceeding the daily limits. At some, but not all, frequencies, the prevalence of dependence also was sig nificantly higher among individuals who exceeded the weekly limits than those who did not (Dawson et al. 2005a). Over the course of a 3year followup interval, a prospective study of U.S. adults revealed that baseline frequency of drinking five or more standard 0.6 oz drinks (for men) or four or more (for women) had a positive linear association with the first incidence of alcohol abuse and dependence that was significant even after controlling for ADV of ethanol intake (Dawson et al. 2008). Individuals who con sumed five or more drinks (men) or four or more drinks (women) on a daily or neardaily basis at the baseline interview had an almost fourfold increase in the odds of incident alcohol abuse and more than a sevenfold increase in the odds of incident dependence.
The criteria in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV; American Psychiatric Association 1994) for alcohol use disorders do not require any minimum level of consumption for a positive classification of abuse or dependence, although a consumption criterion has been proposed as one possible means to tap the less severe range of the latent trait of AUDs (Saha et al. 2007). Rather, alcohol consumption is viewed as a correlate of AUD (both a precursor and an outcome, given the complex reciprocal relationship between the two), and consumption questions have come into increasing use in briefscreening instruments designed to identify indi viduals with AUDs in primary and emergency care settings. Several brief screeners containing both alcohol consumption and alcohol problem items have shown high levels of sensi tivity (the proportion of individuals with the AUD outcome in question who screen positive) and specificity (the proportion of individuals without the AUD outcome in question who screen negative) for AUD and/or haz ardous drinking (Berner et al. 2007;Kelley et al. 2009). These include the Alcohol Use Disorders Identification Test (AUDIT; Saunders et al. 1993) and the Rapid Alcohol Problems ScreenQuantity Frequency (RAPS4 QF; Cherpitel 2002). The AUDITC, containing only the three AUDIT consumption questions on overall frequency of drinking, usual quantity of drinks consumed on drinking days, and frequency of heavy drinking, has proven nearly as effective as the full 10question AUDIT in screening for AUDs and risk drinking in the general population and subpopulations such as veterans and patient samples (Aertgeerts et al. 2001;Bradley et al. 2003;Bush et al. 1998;Dawson et al. 2005b;Gordon et al. 2001;Gual et al. 2002;Rumpf et al. 2002). More recently, studies of a singleitem screening instrument based solely on the frequency of heavy drinking also have reported high levels of sensitivity and specificity in screening for AUDs and risk drinking in trauma center and emergencydepartment samples (Canagasaby and Vinson 2005; Dawson et al. 2010;Seale et al. 2006;Smith et al. 2009;Stewart et al. 2008;Taj et al. 1998;Williams and Vinson 2001). In a sample of U.S. adults, drinking five or more drinks (men) or four or more drinks (women) at least once in the preceding year resulted in a sensitivity and specificity of 86.7 percent and 82.1 percent, respectively, in predicting DSM-IV alcohol abuse and/or dependence (Dawson et al. 2010). Many of the studies of the AUDIT, AUDITC, and other brief screening instruments have noted differential performance across sub groups of the general U.S. population, often supporting lower screening score thresholds for detecting problem drinking among women and the elderly (Berner et al. 2007;Dawson et al. 2005, in press;Kelly et al. 2009). A recent test of a singleitem screener based on maximum drinks consumed likewise found variation across sub groups. By gender, the cut point that maximized sensitivity and specificity for any AUD or any AUD/hazardous drinking was five or more drinks for men and four or more drinks for women (Dawson et al., in press), thus providing support for the gender specific five or more/four or more drinks definition of risk drinking that has come into common use in U.S. surveys of drinking practices and problems (Wechsler and Nelson 2001;Wechsler et al. 1995).

International LowRisk Drinking Guidelines
Perhaps the best illustration of the complexity of defining risk drinking can be obtained by comparing interna tional drinking guidelines. A number of countries have systematically formu lated lowrisk drinking guidelines with the input of expert committees of researchers who have conducted exten sive reviews of the scientific literature. By providing the upper limits of low risk drinking, these guidelines implic itly reveal various countries' definitions of risk drinking (i.e., consumption beyond the lowrisk limits). Two reports describing recent changes to the Australian and Canadian drinking guidelines provide the rationales used for setting the guidelines in those countries. They illustrate the broad range of evidence typically considered in establishing these guidelines and the diverse approaches (e.g., relative versus absolute risk) that may be applied to the interpretation of this evidence (National Health and Medical Research Council, http://www. nhmrc.gov.au/_files_nhmrc/file/public ations/synopses/ds10alcohol.pdf; Stockwell et al., in press).
Lowrisk drinking guidelines vary substantially across countries, as is evident in an online listing of these guidelines that is continually updated (see http://www.icap.org/Publications/ ICAPReports/tabid/75/Default.aspx). The various guidelines differ among countries not only in terms of the maximum permissible numbers of drinks but also in terms of what types of limits are included (daily, weekly, or both) and whether there are different guidelines for men and women (see table). Although most countries' drinking guidelines are expressed solely in terms of daily limits, Denmark, Finland, Ireland, and South Africa have weekly drinking limits only. Canada, New Zealand, Poland, the United Kingdom, and the United States include both daily and weekly limits. Australia and Slovenia provide limits for consumption on "any day" (which when multiplied times seven roughly correspond to weekly limits), with higher limits for any single drinking occasion. The Australian guidelines explicitly state that the former are targeting the risk of chronic conditions and the latter the acute consequences of heavy drink ing. The United States, Canada, Italy, and South Africa all have definitions of moderate drinking that are more restrictive than their thresholds for lowrisk drinking, and Spain's guide lines include regional variations (i.e., considerably higher limits in the Basque country and Catalonia than in the overall national guidelines). In general, lowrisk drinking guidelines stipulate the upper limit of lowrisk consumption, but a few countries (i.e., Japan, Portugal, Romania, Spain [Catalonia], the United Kingdom, and the United States [Dietary Guidelines moderate drinking defini tion for men]) provide a range of acceptable values.
Many of the differences across countries in the specific numbers of drinks comprising daily or weekly limits reflect variation in the standard drink size used to express the daily and/or weekly limits. The standard drink size assumed by the U.S. drink ing guidelines (0.6 oz or approximately 14 g of ethanol) is almost twice as large as the standard drink size of 8 g used by the United Kingdom. A stan dard drink size of 10 g is used in Australia and most of Europe other than the United Kingdom; the Canadian standard drink size is 13.45 g. Japan lies at the upper extreme, with a stan dard drink size of 19.75 g. For a full description of international variation in standard drink size, see http://www. icap.org/table/InternationalDrinking Guidelines and DevosComby and Lange (2008). However, even when expressed in the common metric of grams per day or week, the upper limits of lowrisk drinking vary con siderably across countries. Daily limits for men vary from a low of 20 g in Poland and Sweden to a high of 70 g in the Basque country of Spain and those for women vary from 10 g in Poland to 70 g in the Basque country. Weekly limits for men lie in the range of 100 g in Poland to 252 g in Denmark and South Africa, whereas those for women lie in the range of 50 g in Poland to 168 g in Denmark and South Africa.
Australia, Canada, France, Italy, Romania, Singapore, Spain (all regions), Sweden, and Switzerland have identi cal lowrisk drinking guidelines for men and women, although Italy also has a set of Nutritional Guidelines with complex moderate drinking recommendations based on total body weight that generally would yield higher limits for men than women. The Canadian guidelines from the Center for Addiction and Mental Health have identical daily limits for men and women but lower weekly limits for women. Japan has guide lines for men only. The remaining countries for which guidelines are available-Austria, Canada (National Alcohol Strategy Advisory Committee), the Czech Republic, Denmark, Finland, Germany, Ireland, the Netherlands, Poland, Portugal, Slovenia, South Africa, the United Kingdom, and the United States) have different drinking limits for men and women in all components of their lowrisk drink ing guidelines. Typically, the gender differences in the daily limits are proportionately smaller than those in the weekly limits.
There have been surprisingly few attempts to validate individual coun tries' drinking guidelines against spe cific outcomes. In a crosssectional analysis of the U.S. drinking guide lines among pastyear drinkers, Dawson (2000a) found that exceeding the weekly limits or having ever exceeded the daily limits in the past year yield ed high sensitivity for alcohol depen dence, impaired driving, liver disease, peptic ulcer, and hypertension (64.3 percent to 98.5 percent), but that specificity was extremely low (28.7 percent to 32.5 percent) for these outcomes. Specificity was improved (72.0 percent to 76.1 percent) at a higher frequency of exceeding the daily limits (at least once a week), but sensitivity was accordingly reduced (30.8 percent to 70.6 percent). In multivariate models adjusted for sociodemographic characteristics, the odds of all of the outcomes except for peptic ulcer were significantly increased among drinkers who exceeded the weekly or daily limits, regardless of the frequency of the latter. It is inter esting to note that the odds ratios virtually were identical when consider ing only whether the drinkers exceed ed the daily limits. That is, little additional information on risk was obtained by considering the weekly as well as daily limits. A more recent evaluation of the U.S. guidelines con sidered pastyear alcohol consumption relative to multiple concurrent and prospective harms and found that the thresholds that optimized prediction of concurrent harm (i.e., the upper limits of what might be considered lowrisk drinking) consisted of 4 drinks a day for men and 3 drinks a day for women (4/3), alone or in combina tion with weekly limits of 21 drinks for men and women. Prospective harms were best predicted by weekly limits of 14/7 (men and women, respectively), 14/14 and 10/10 drinks, all combined with daily limits of 4 drinks for both men and women (Dawson et al., in press). Using a prospective framework, Batty and colleagues (2009) recently examined the effect of exceeding the daily and weekly U.K. drinking limits on the occurrence of various harms over the course of a 3.6year followup inter val. They reported that exceeding the daily limits was associated with an increased risk of hypertension, whereas exceeding the weekly limits was asso ciated with an increased risk of financial problems. Of interest is a nearsignificant association with accidents occurred with respect to exceeding the weekly rather than daily limits, suggesting that the intheevent levels of con sumption typically associated with injuries did not significantly increase the risk of accidents unless they were consumed often enough to yield a volume of intake that exceeded the weekly drinking limits.

The Effect of Drink Size on Definitions of Risk Drinking
Despite the abundant evidence of chronic and acute alcoholrelated harm at various levels of average daily or per occasion ethanol intake, converting risk thresholds into a comprehensible defi nition of risk drinking must ultimately confront the issue of drink size. The amount of ethanol contained in an alcoholic drink varies considerably depending on the type of alcohol (e.g., beer, wine, or spirits) and on the size of the drink. Within the major categories of alcoholic beverages, there are significant variations according to beverage subtype. Malt liquor, with a typical ethanol con tent of at least 6.0 percent alcohol by volume (ABV), is far stronger than light beer, with a typical ABV of about 4.2 percent. Likewise, fortified wines have an ABV that is about 50 percent greater than that of regular table wine or champagne, approximately 18 percent versus 12 percent (Kerr et al. 2006a).
Moreover, spirits such as whiskey, vodka, and gin have an ABV that is greater than that of cordials and liqueurs and far greater than that of prepackaged cocktails (Kerr et al. 2006b Unfortunately, all evidence suggests that this is not the case. In an exhaus tive review of 32 studies related to drink size published through 2007, DevosComby and Lange (2008) found that drinkers often were unaware of how standard drinks were defined in their countries and that actual drink sizes (or attempts to pour a standard drink) often exceeded standard drink sizes. The magnitude of the discrepancy varied substantially across studies and was associated with study design, drinker characteristics, type of beverage, and vessel size. More recent U.S. research confirmed that vessel size was more important than shape in determining the size of drink pours (Kerr et al. 2009a) and that largerthanstandard drinks were common even in bar and restaurant drinks (Kerr et al. 2008). Although largerthanstandard drink sizes are the major concern in the prevention of risk drinking, it should be noted that a significant proportion of drinkers consume smallerthanstandard drinks. In fact, colleagues (2005, 2009b) have shown that there is a great deal of dispersion in the distribution of actual drink sizes and that the degree of dispersion varies by beverage (smallest for beer and larger for wine and spirits) and by demo graphic characteristics (smaller for men and Whites and larger for women and minorities). Thus, it must be understood that many drinkers will interpret drinking guidelines in terms of numbers of drinks that correspond to levels of intake that are smaller or larger than those intended by the standard drink definitions included in the guidelines. In light of this, it might be argued that standard drink sizes for any given country should reflect the most common container or serve sizes in that country, even if this leads to lack of comparability across countries. That is, the standard drink definitions that maximize pre vention efforts may not be those best suited for comparative research pur poses. Research addressing how guidelines are understood by drinkers who typically pour nonstandard drinks might help to improve the delivery of drinking guidelines to these individuals.

Conclusions
Definitions of risk drinking, as implied by the lowrisk drinking guidelines of the United States and other countries, are generally in line with levels of risk observed in the scientific literature. Although estimated associations of alcohol consumption with allcause mortality and chronic disease vary as a function of level of adjustment and reference group, the ADV at which an increased risk of mortality is apparent generally lies in the range of 35 g to 45 g, or 245 g to 315 g per week, and the risk of many chronic medical con ditions is significantly increased (albeit quite modestly in many cases) at ADVs as low as 25 g, or 175 g per week. The weekly drinking limits for the majority of countries lie within this range. Evidence for gender differences in the association of drinking volume and chronic harm is both sparse and incon sistent but suggests that risk thresholds may be somewhat lower for women than men, at least for some conditions. The quite substantial differences in men's and women's weekly drinking guidelines in a number of countries, including the United States, with limits of 196 g and 98 g, respectively, are not fully supported by the existing data. They are more consistent with an influential early analysis of alcohol and allcause mortality conducted by English and colleagues (1995), which reported modest but significant increases in allcause mortality at an ADV of 20 g for women compared with 40 g for men. It is important to bear in mind that many of the mortality and chronic disease studies summarized previously were large prospective stud ies that collected information on numerous risk factors for disease and mortality. Estimated volume of ethanol intake may be based on minimal data and sometimes represents nothing more than the product of a single ques tion on drinking frequency times a single question on usual or average number of drinks consumed on days when drunk. As a result, any given ADV is probably an underestimate, and the harm associated with specific ADV levels is therefore likely associated with what is actually a larger ADV.
Acute alcoholrelated harm generally shows a linear increase with drinking in the event and frequency of HED, sometimes with a threshold effect (i.e., an attenuation or evening off of the slope of the risk curve after a certain number of drinks or HED frequency). Linear risk curves provide no obvious basis for determining the cutoff corresponding to risk drinking, which may help to explain the wide range of daily drinking limits in international lowrisk drinking guide lines. Moreover, the data as related to gender differences in the association of acute alcoholrelated harm and drinking are highly inconsistent across studies. In part, these inconsis tencies may reflect gender differences in the underlying probability of the type of acute harm being studied, (e.g., the greater tendency of men to engage in violent behavior irrespective of drinking level). This raises questions as to whether riskdrinking definitions for men and women should reflect gender differences in the underlying harm probabilities themselves or rather in the extent to which these probabilities are modified by drinking (Dawson 2009). One solution to this issue is to key riskdrinking definitions (and lowrisk drinking limits) to ethanol intake levels corresponding to psy chomotor impairment, an approach that helped to inform the NIAAA lowrisk daily drinking limits (see table). It is worth noting that the U.S. drinking limits, especially those for men, are among the highest interna tionally. In part, this may reflect the fact that the current standard drink size of 0.6 oz or 14 g, slightly larger than the standard drink size of approximately 12 g that was assumed at the time those guidelines were first drafted. In addition, the riskdrinking definition of five or more drinks (men) or four or more (women) underlying the NIAAA daily drinking limits has proven optimal in its ability to identify individuals with AUDs, an outcome of obvious importance to NIAAA (National Institute on Alcohol Abuse and Alcoholism 1998) and a type of alcoholrelated harm that may have been given less weight in the con struction of other countries' drinking guidelines. One final note of caution is with respect to applying scientific evidence to daily drinking limits. The nearuniversal use of five or more drinks (men) or four or more drinks (women) as a measure of HED (or their equivalent in countries with smaller standard drink sizes) means that few studies have been able to evaluate whether some other measure of HED would be more strongly asso ciated with harm. Likewise, when measures are inherently gender based, such as the definition of HED using five or more drinks (men) or four or more drinks (women), this precludes testing for the significance of gender differences in the relationship between HED and alcoholrelated harm.
Questions about how best to convey the definition of risk drinking to the public remain even after evidence based riskdrinking limits have been established. As is evident from a review of international drinking guidelines, the United States is among a minority of countries that define risk drinking both in terms of daily and weekly consumption. It is arguable that daily limits alone would be sufficient. The logic for such an argument is that most U.S. drinkers are not daily drinkers but rather consume alcohol primarily on weekends and special occasions (NIAAA 1998). Given such a pattern of intake, individuals who adhered to lowrisk daily drinking limits would not exceed weekly limits simply because they would have too few drinking occasions to do so. However, drinking patterns vary over the life course, with most data indicating increasing frequency of drinking in lower quantities in relation to aging (Dawson 2000b). This being the case, weekly limits, or a definition of risk drinking that includes weekly consumption, may be useful for the growing number of drinkers aged 55 and older among the aging Baby Boomers in the United States.
Regarding the perplexing and chal lenging issue of drinkers' inability to accurately gauge their consumption in standard drinks, the most obvious solution lies in the approach that has been adopted by a number of Western countries, in which alcoholic beverage containers explicitly state how many standard drinks ("units") they contain. Even in the absence of such labeling, it has been argued that if risks attributed to drinking five or more drinks are based on scientific evidence relying on actual as opposed to standard drink sizes, coupled with other sources of consumption underreporting, then drinking less than five drinks, irre spective of how closely they correspond to standard drink size, will reduce harm in the aggregate. That is, if one assumes that relative risks associated with various consumption levels are overstated because of underreporting of consumption, then adherence to lowrisk drinking limits should prove effective even for individuals whose actual drink sizes are larger than stan dard. Hence, publicizing lowrisk drinking limits should play an impor tant role in any activities aimed at preventing alcoholrelated harm. ■